ETG is easily the most beautiful pixel art game that came out since FEZ. Especially given the random nature of the game, it makes the work all that much more impressive (and this is not mentioning the awesome animation work, which gives everything so much personality).

Isaac has that functional look and the game ends up having much more focus on a sort of "creative" design which makes it very unique and beautiful in its own way. Where ETG has a design focus on more traditional aspects, such as graphics and moment to moment gameplay.

I mean, you can clearly see the difference of focus between the games: ETG has pixel alignment rendering and BOI has sprite rotation and scaling, which breaks completely the pixel graphics and gives it that cheap look. However, you can see the effect of items on your character itself, and each item changes in a way or another the way you play (well, unless you get a range upgrade when you already have enough range): It is the signature and the key point of Isaac, and this is why people spend so much time into that game, and where comes the "replayability".

To add to it, this is part of the reason BOI looks bad compared to ETG: the colors that are displayed on screen in ETG are carefully controlled, your bullets are yellow, the enemy bullets are red, and the environment and enemy colors are selected. In BOI, the environment palette is monochrome, which gives way more focus on your tears and character, and pushes that idea of a "your own construction" type of game. ETG allows itself a more dynamic palette with 2 or 3 colors per floor.

There is also a lot to be said about the differences in camera movement, room size and music choices, but I already rambled enough here.

I find it interesting to compare BOI to ETG on artistic aspects, it is good to see how games can suck hundreds of hours from people, and great to understand what inspires people in the same way in yet such different games.